Sclabas Guido M, Fujioka Shuichi, Schmidt Christian, Evans Douglas B, Chiao Paul J
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Int J Gastrointest Cancer. 2003;33(1):15-26. doi: 10.1385/IJGC:33:1:15.
Although the genetic profile of pancreatic cancer is emerging as a result of much research, the role of specific genetic alterations that initiate tumorigenesis and produce its cardinal clinical features of locally aggressive growth, metastasis, and chemotherapy resistance remains unresolved. Recently, a number of studies have shown that the inhibition of constitutive NF-kappaB activation, one of the frequent molecular alterations in pancreatic cancer, inhibits tumorigenesis and metastasis. It also sensitizes pancreatic cancer cell lines to anticancer agent-induced apoptosis. Therefore because of the crucial role of NF-kappaB in pancreatic cancer, it is a potential target for developing novel therapeutic strategies for the disease. In vivo and in vitro models that mimic the tumorigenic phenotypes in the appropriate histological and molecular concert would be very useful for confirming the suspected role of the pancreatic cancer signature genetic lesions and better understanding the molecular basis of this disease.
尽管经过大量研究，胰腺癌的基因图谱已逐渐明晰，但启动肿瘤发生并产生其局部侵袭性生长、转移和化疗耐药等主要临床特征的特定基因改变所起的作用仍未明确。最近，多项研究表明，抑制组成型NF-κB激活（这是胰腺癌中常见的分子改变之一）可抑制肿瘤发生和转移。它还使胰腺癌细胞系对抗癌药物诱导的凋亡敏感。因此，由于NF-κB在胰腺癌中起着关键作用，它是开发该疾病新型治疗策略的潜在靶点。在适当的组织学和分子协同作用下模拟致瘤表型的体内和体外模型，对于确认胰腺癌标志性基因损伤的推测作用以及更好地理解该疾病的分子基础将非常有用。
